The purpose of this K23 proposal is to allow for my continued development as a clinical researcher with the goal of becoming an independent leader in the investigation of interstitial lung disease. Under the mentorship of Dr. Talmadge E. King, Jr. and Dr. Michael A. Matthay, and with guidance from a network of experienced clinical and basic researchers, I will obtain the experience and skills necessary to achieve this goal. The research proposal I have designed involves defining acute exacerbations of Idiopathic Pulmonary Fibrosis (IPF) at a clinical and biological level. IPF is a common and highly morbid form of interstitial lung disease, of which acute exacerbations are an important component. The incidence, causes, and clinical significance of acute exacerbations remain poorly understood. Recently, the NHLBI has created the IPF Clinical Research Network (IPFNet) to allow for large-scale, well-designed interventional studies of IPF. By positioning my research proposal to take advantage of IPFNet subjects and infrastructure, I plan to achieve the following four specific aims: Aim 1: To determine the incidence of and risk factors for acute exacerbations of IPF. Aim 2: To define the etiologic role of occult viral infection in acute exacerbations of IPF. Aim 3: To determine the role of disordered coagulation in acute exacerbations of IPF. Aim 4: To demonstrate the prognostic significance of acute exacerbations of IPF. To achieve these aims, clinical data, respiratory secretions, and blood samples will be collected from an estimated 150 subjects with acute exacerbations of IPF and appropriate controls. This research proposal may provide insight into the frequency and causes of acute exacerbations, providing evidence upon which to design interventional trials of prevention and treatment. Importantly, this research proposal will also serve to foster my career development goals of gaining experience and expertise in conducting prospective clinical research trials, mastering sophisticated biostatistical techniques, and developing multidisciplinary collaborations among clinical and basic scientists. These skills will allow me to fully realize the power of clinical research to inform basic biology and advance medical knowledge. [unreadable] [unreadable] [unreadable]